(1) Field of the Invention
This invention relates to a novel influenza vaccine, in particular to an influenza vaccine consisting of artificial vesicle-like particles of a complex of HANA antigen derived from influenza virus, known as the active component of the vaccine, and a muramyldipeptide derivative (hereunder referred to as MDP derivatives) known as synthetic adjuvant, the artificial particles being similar in size and shape to naturally occurring influenza virus particles. This invention also relates to a process for preparing such a novel vaccine.
(2) Description of the Prior Art
Since the vaccination effect of presently used influenza HA vaccines is subject to fluctuation by mutations which occur on HA (hemagglutinin) molecule of the prevailing virus, it is strongly desired to develop more effective vaccines than the conventional ones.
One of the recent approaches in influenza vaccine development is directed to a component vaccine consisting of HA and NA (neuraminidase) as the main ingredients, i.e., influenza HANA vaccine. The resulting vaccine comprised of purified HA and NA is considered an ideal vaccine in terms of safety and effect and has already been put to practical use in England. Actually, however, the effect of the vaccine is still insufficient.
On the other hand, another approach is directed to utilization of adjuvants. This work has resulted in the development of muramyldipeptide (MDP) as well as many kinds of MDP derivatives which improved on the immunopotentiation and the like of MDP by appropriate chemical modification, as novel adjuvant materials. Regarding these MDP derivatives, it is, for example, reported by Kotani et. al., in YAKUGAKU ZASSHI 103(1), 1-27, 1983 that 6-0-(2-tetradecylhexadecanoyl) MDP was administered to guinea pigs together with influenza vaccine (i.e., HANA vaccine) containing highly purified HA and NA as main ingredients, and that effective adjuvant effect was obtained. However, HANA vaccine obtained by simply adding these MDP derivatives into a vaccine as an adjuvant does not provide the vaccine with adequate effect.